Piconol → 5-Amino-1-(4-fluorophenyl)-4-[3-(pyridin-2-ylmethoxy)benzoyl]pyrazole

HRID 1278882Notes

Reaction equation

HRID 1278882 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14](=[O:22])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([OH:21])[CH:16]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH2:29]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1(C)C=CC=CC=1>[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14](=[O:22])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:29][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=2)[CH:16]=1

Participants

6

Reactant 4

HCID 11474PiconolHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 115439135-Amino-1-(4-fluorophenyl)4-[3-hydroxybenzoyl]pyrazole

Product 1

HCID 98650945-Amino-1-(4-fluorophenyl)-4-[3-(pyridin-2-ylmethoxy)benzoyl]pyrazole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

5-Amino-1-(4-fluorophenyl)-4-[3-hydroxybenzoyl]pyrazole, from Example 10, step 2, (0.5 g, 1.68 mmol), 2-pyridylcarbinol (0.81 mL, 8.41 mmol), triphenylphospine (1.81 g, 6.9 mmol), and diethylazodicarboxylate (1.09 mL, 6.9 mmol)) were combined in toluene (50 mL). The reaction mixture was stirred for 16 hours then quenched with a saturated aqueous solution of NH4Cl and extracted three times with ethyl acetate. The product was then extracted from the ethyl acetate into a 10% aqueous solution of HCl. The aqueous layer was then neutralized with NaOH and extracted with ethyl acetate. The organic extracts were dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by column chromatography on silica gel using 1:1 hexane/ethyl acetate to give 0.165 g of 5-amino-1-(4-fluorophenyl)-4-[3-(pyridin-2-ylmethoxy)benzoyl]pyrazole (mpt. 176.1-177.3° C.).

Workup

  1. customthen quenched with a saturated aqueous solution of NH4Cl
  2. extractionextracted three times with ethyl acetate
  3. extractionThe product was then extracted from the ethyl acetate into a 10% aqueous solution of HCl
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by column chromatography on silica gel using 1:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-45015f4abb504e79b0c1b82a34bfa7b5
Source dataset
uspto-grants-2002_09
Patent number
US06444696B1

Reaction notes

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